PAH: market ripe for expansion as big pharma interest increases

No consensus currently exists as to the actual prevalence of PAH. Most physicians and sources agree that the PAH population falls between 40,000 and 100,000 people, with companies interested in the PAH market citing US prevalence rates of 50,000. However, according to a new report, there are approximately 146,000 people suffering from PAH across the seven major markets, with the majority of these patients (47%) in .

Overview of PAH

Simply put, PAH is continuous high blood pressure in the pulmonary artery. The average blood pressure in a normal pulmonary artery is about 14mmHg at rest; in PAH, this pressure can almost double, with average pressures of around 25mmHg not uncommon.

The physiological changes that occur as a result of PAH, while mercifully rare, can have a huge impact on quality and duration of life. Tightening and thickening of the muscles within the walls of the pulmonary arteries are the most common manifestations, with blood clots also being an issue due to hemodynamic disturbances. Despite treatments being available, there is still huge clinical unmet need in this disease.

Big pharma interest despite orphan disease status

The PAH market has received significant interest in the past two years, despite the disorder's status as an orphan disease. This interest was sparked by the launch of three new therapies and formulations in the US - United Therapeutics' IV Remodulin (treprostinil), CoTherix' Ventavis (iloprost), and Pfizer's Revatio (sildenafil) - and the potential for significant additional product launches over the next three years.

Although a rare, orphan disease, commercial interest in PAH has increased in the past year. PAH's status as an orphan disease confers on it considerable financial and regulatory incentives, making it attractive to pharmaceutical and biopharmaceutical companies.

In addition, the medical community has made significant advances in understanding the etiology and pathophysiology of PAH. Finally, the publication of guidelines regarding the treatment of PAH is increasing awareness of the disease in the medical community. Although several PAH compounds have reached late-stage development, considerable opportunity remains.

Of the 146,000 patients thought to be suffering from PAH globally, only a quarter to a third are actually diagnosed and treated, creating significant room for growth in the number of patients treated with PAH therapies over the next decade. As such, the number of treated patients at a more advanced stage of the disease is expected to nearly double from 2006-14.

Three's company in a dynamic market

There are currently five approved treatments for PAH that fall into three main classes: endothelin receptor antagonists (ERAs), phosphodiesterase-5 (PDE-5) inhibitors and prostacyclins. Using gold-standard IMS sales data, Datamonitor estimates that the global PAH market reached $636 million in 2004, driven mainly by sales of Actelion's Tracleer (bosentan) and GlaxoSmithKline's (GSK's) Flolan (epoprostenol), which generated sales of $362 million and $193 million, respectively. Both products combined command 87% of the market.

Despite being considered the gold standard for treating more severe cases of PAH, GSK's Flolan has come under increased commercial competition, both from other, more conveniently dosed, prostacyclins, such as United Therapeutics' IV Remodulin, and the orally active ERAs and PDE-5 inhibitors.

"While physicians largely prefer Remodulin for its convenience, experience with Flolan and general opinion that the drug is more efficacious will soften the decline in Flolan revenues, even as Remodulin revenues experience strong growth. As such, Datamonitor expects Remodulin to become the worldwide prostacyclin class leader in 2007."

In addition, much of the shift in market dominance toward the ERAs has come about due to the commercial success of Actelion's Tracleer. However, Tracleer is expected to come under significant competitive pressure over the next three years, as it faces the launch of two next-generation ERAs and additional oral agents for the treatment of PAH.

Encysive's Thelin (sitaxentan) is expected to gain an approval in 2006, followed by Myogen's ambrisentan in 2007. Both have the potential to become best-in-class, but that does not spell the end for Tracleer, which is still a worthwhile competitor in a rapidly growing market due to its longer track record and ability to prevent worsening of the disease.

Moving forward, it appears that, among developmental treatments for PAH, only one drug in the ERA class has the potential to generate sales in excess of $500 million, namely Myogen's ambrisentan. Based on its early data, ambrisentan may have the most attractive overall clinical profile among the three leading ERAs; low liver toxicity, no interaction with warfarin or sildenafil, and potentially better efficacy than Tracleer and Thelin will all contribute to ambrisentan's success. Indeed, it would be no surprise to see ambrisentan hits sales of $500 million annually by 2014.

Historic success will shape future trends

With the maxim 'if it ain't broke, don't try and fix it' ringing firmly in their ears, the pharmaceutical players interested in the PAH market are being conservative in development terms. Many of the new products in development for the treatment of PAH are focused on currently successful modes of action, particularly the ERAs, which are expected to command nearly 60% of the PAH market by 2014.

Much of the developmental activity in PAH is focused on next-generation ERAs and the lifecycle management of currently marketed PDE-5 inhibitors, such as tadalafil, the active ingredient in Eli Lilly's Cialis. Moreover, many of the new kids on the block will be used as add-on therapies as none are currently providing a significant improvement on what's currently available.

Market ripe for expansion

As a result of the increased level of interest in PAH from big pharma, the PAH market looks set to triple in value over the forecast period. Between 2004 and 2014, the PAH market is predicted to grow from $636 million to just over $2 billion, representing a CAGR of 11%.

Most of this growth is expected to come from pipeline products, with Myogen's next-generation ERA, ambrisentan, expected to become the market leader with sales in excess of $500 million by 2014.

Increased diagnosis and treatment rates are expected and, as such, the market is ripe for expansion. Manufacturers of the next-generation ERAs will come out top dogs in the long-run, as these drugs have convenient dosing and good safety and efficacy. As for the PDE-5 inhibitors, PAH is not a key area of focus for Pfizer and Eli Lilly. As such, sales of Revatio and tadalafil will need to rely on physician sentiment rather than marketing muscle.

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